Teneurin c-terminal associated peptides (tcap) and methods and uses thereof

Abstract

The invention provides a novel family of biologically active neuropeptides and the nucleic aid molecules coding for same. The peptides are derived for the C-terminus of the teneurin family peptides (Ten M1-4). These novel peptides, referred to as teneurin C-terminal associated peptides (TCAPs) are active in neuronal communication and are implicated in a number of neuropathologies. They are particularly useful in modulating stress responses and anxiety and in the treatment of cancer.

1 - 34 . (canceled) 
     
     
         35 . A method of modulating and/or regulating a stress response comprising administering to a cell or subject in need thereof an effective amount of a teneurin c-terminal associated peptide (TCAP peptide), or a pharmaceutically acceptable salt thereof, wherein the amino acid sequence of said TCAP peptide consists essentially of:
 (i) an amino acid sequence having an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 21, 22, 29, 30, 37, 38, 45, 46, 53, 54, 61, 62, 69, 70, 77, 78, 85, 86, 93, 94, and 101   optionally wherein:   (a) the carboxy terminal end of the peptide is amidated or further comprises an amidation signal sequence; and/or   (b) wherein the amino terminal amino acid of the peptide is glutamine, the glutamine is in the form of pyroglutamic acid.   
     
     
         36 . The method of  claim 35  wherein the TCAP peptide consists essentially of:
 (i) an amino acid sequence selected from the group consisting of SEQ ID NOs: 37, 38, 69, 70, and 101; 
 optionally wherein: 
 (a) the carboxy terminal end of the peptide is amidated or further comprises an amidation signal sequence; and/or 
 (b) wherein the amino terminal amino acid of the peptide is glutamine, the glutamine is in the form of pyroglutamic acid. 
 
     
     
         37 . The method of  claim 35  wherein the TCAP peptide consists essentially of:
 (i) an amino acid sequence having an amino acid sequence selected from the group consisting of SEQ ID NOs: 37, 38, 69, and 70; wherein the carboxy terminal end of the peptide is amidated or further comprises an amidation signal sequence; and optionally wherein the amino terminal amino acid of the peptide is glutamine, the glutamine is in the form of pyroglutamic acid. 
 
     
     
         38 . The method of  claim 35  wherein the TCAP peptide consists essentially of:
 (i) an amino acid sequence having an amino acid sequence selected from the group consisting of SEQ ID NOs: 53, 54, 85 and 86; 
 optionally wherein: 
 (a) the carboxy terminal end of the peptide is amidated or further comprises an amidation signal sequence; and/or 
 (b) wherein the amino terminal amino acid of the peptide is glutamine, the glutamine is in the form of pyroglutamic acid. 
 
     
     
         39 . The method of  claim 38  wherein the carboxy terminal end of the peptide is amidated or further comprises an amidation signal sequence; and optionally wherein the amino terminal amino acid of the peptide is glutamine, the glutamine is in the form of pyroglutamic acid. 
     
     
         40 . The method of  claim 39  wherein when the amino terminal amino acid of the peptide is glutamine, it is in the form of pyroglutamic acid. 
     
     
         41 . The method of  claim 35  for preventing or treating a stress response by administering and effective amount of the peptide or pharmaceutically acceptable salt thereof to a subject who is or may be exposed to a stressor or be experiencing a stress response. 
     
     
         42 . The method of  claim 35  wherein the stressor is cell proliferation and the administration of an effective amount of the peptide or pharmaceutically acceptable salt thereof to a subject in need thereof inhibits cell proliferation. 
     
     
         43 . The method of  claim 42  wherein the stressor is aberrant regulation of neuronal growth and administration of the effective amount of the peptide or pharmaceutically acceptable salt thereof is to a subject experiencing aberrant regulation of neuronal growth to inhibits cell proliferation of the neuronal growth. 
     
     
         44 . The method according to  claim 42  wherein the cell is selected from the group consisting of neuronal or fibroblast cells and the peptide or pharmaceutically acceptable salt thereof is administered to a subject with aberrant regulation of neuronal or fibroblast cells to inhibit proliferation of said cells. 
     
     
         45 . The method of  claim 42 —for wherein the cell proliferation is associated with tumour growth and the peptide or pharmaceutically acceptable salt thereof is administered to a patient with a tumour to inhibit tumour growth and/or metastasis of the tumour. 
     
     
         46 . The method of  claim 45  wherein the tumour is a human breast cancer or a neuroblastoma and the effective amount of the peptide or pharmaceutically acceptable salt thereof is administered to a subject with breast cancer or a neuroblastoma to inhibit proliferation and/or metastasis of the breast cancer or neuroblastoma. 
     
     
         47 . The method of  claim 35  wherein the stressor is a physiological stressor and wherein administration of the effective amount of the peptide or pharmaceutically acceptable salt thereof to a cell or subject exposed to a physiological stressor inhibits damage caused by physiological stressor by protecting cells in vitro or in vivo from the physiological stressors by inhibiting cell proliferation. 
     
     
         48 . The method of  claim 35  wherein the stress response is anxiety and the effective amount of the peptide or pharmaceutically acceptable salt thereof is administered to a subject in need thereof to prevent or treat anxiety. 
     
     
         49 . The method of  claim 50  wherein administration of the peptide or pharmaceutically acceptable salt thereof to the subject in need thereof normalizes the anxiety response. 
     
     
         50 . The method of  claim 50  wherein when the subject is a low anxiety subject, normalizing the anxiety response comprises increasing anxiety or inducing an anxiogenic response in the low anxiety subject. 
     
     
         51 . The method of  claim 50  wherein when the subject is a high anxiety subject, normalizing the anxiety response comprises decreasing anxiety or inducing an anxiolytic response in the high anxiety subject. 
     
     
         52 . The method of  claim 50  wherein the subject is a normal anxiety subject and normalizing the anxiety response comprises maintaining a normal anxiety response in the normal anxiety subject.